The cyst(e)ine nutritional requirement of leukemic and normal lymphoid cells in vitro has been determined here at the Sidney Farber Cancer Center. Investigations by Foley, Lazarus, and Livingston have revealed a decreased cyst(e)ine biosynthetic capability of malignant lymphoid cells as compared to their normal counterparts. This quantitative difference in cyst(e)ine synthetic ability should impose an increased dependence on plasma cyst(e)ine levels for growth by the neoplastic cells. Consequently, plasma cyst(e)ine depletion brought about by the injection of a cyst(e)ine degrading enzyme should show preferential inhibition of malignant cell growth with little accompanying host toxicity. We propose to isolate and characterize cyst(e)ine-degrading enzymes with suitable kinetic and pharmacologic properties for use in vivo. Enzymes which have the ability to create a rapid in vivo cyst(e)ine depletion will be evaluated for their antineoplastic efficacy. Studies also will be initiated to optimize enzyme therapy by combination studies with low molecular weight inhibitors of host cyst(e)ine biosynthesis and by chemical modification of enzyme antigenicity and clearance properties.